Director of Clinical Proteomics & Senior Principal Scientist Genentech, California
Biomarkers are indispensable tools in drug development, offering crucial insights into target engagement, dose selection, and candidate therapeutic mechanisms. Liquid chromatography-mass spectrometry (LC-MS) stands uniquely positioned to facilitate accurate quantitation of both small and large molecule biomarker candidates. However, the translation from biomarker discovery to a multiplexed targeted multiple reaction monitoring (MRM) panel to measure samples from large clinical cohorts is often a protracted and resource-intensive process. Furthermore, the challenge of biomarker replication in validation cohorts remains a significant hurdle. In recent years, data-independent acquisition mass spectrometry (DIA-MS) has emerged as a promising approach to streamline translational proteomics for biomarker development. DIA-MS offers numerous benefits, including reproducible label-free analysis of a wide range of samples, the ability to capture low abundance ions across a high dynamic range, and comprehensive proteome coverage. By enabling an unbiased analysis of complex samples, DIA-MS holds immense potential for enhancing biomarker discovery and validation efforts. Notably, the quantitative range for most DIA-MS methods has not been thoroughly characterized, leading to controversies in quantitative conclusions from previous studies. To address these issues, we investigated the quantitative capabilities of DIA-MS methods and established guidelines for quantitative criteria tailored to analysis of samples from clinical trials. Results from clinical biomarker studies in patients with lupus nephritis, inflammatory bowel disorder, and Alzheimer's disease will be discussed. DIA-MS holds immense promise in advancing drug development by uncovering valuable biomarkers that can drive more effective therapeutic interventions.
Learning Objectives:
Upon completion the participants will be able to understand the advantages and challenges of using data-independent acquisition mass spectrometry (DIA-MS) as a promising approach for biomarker discovery and development in drug development.
Upon completion the participants will be able to learn about the potential of DIA-MS in providing comprehensive proteome coverage, capturing low abundance ions, and enabling unbiased analysis of complex samples, leading to enhanced biomarker validation efforts.
Upon completion the participants will acquire knowledge around quantitative criteria for analyzing samples from clinical trials using DIA-MS, as demonstrated through clinical biomarker studies in patients with lupus nephritis, inflammatory bowel disorder, and Alzheimer's disease.